The mouse pituitary tumor cell line AtT-20/D16-16 is an excellent model to study the physiological regulation of synthesis, storage and secretion of ACTH and Beta-endorphin. Initial studies focussed on the characterization of the secretary response to stimulants such as the recently available synthetic 41-residue corticotropin-releasing factor (CRF) and to antagonists such as glucocorticoids. The CRF secretory effect is calcium-dependent and rapid cyclic AMP synthesis is associated with hormonal excitation. CRF was found to stimulate phospholipid methylation in AtT-20 cells, a reaction which appears in other cell systems as an important transducing mechanism following hormone-receptor interaction. Post-translational modification of protein by carboxylmethylation has been implicated in exocytotic secretion in both endocrine and exocrine glands and similar operative mechanisms stimulated by CRF are found in the AtT-20 cell.